Mononuclear phagocytes play a major role in host defense. These cells have numerous functions, many of which can be exposed only after the cells have been stimulated. Much of the knowledge of how cell function can be enhanced has not been applied to complement production by these cells. Stimulated cells spread rapidly on glass or plastic substrates. Changes in function of mononuclear phagocytes may be mediated through effects on cell spreading. This concept is supported by several studies with human monocytes. But the role of cell spreading in the initiation of C2 synthesis (and most other macrophage functions) has not been thoroughly investigated, especially how cell spreading relates to the release of cells to LPS on lymphokine. Much of the knowledge obtained from the in vitro experiments on stimulation of cells has not been applied in animal and human models. We plan to study C synthesis by two types of "resting cells", human peripheral blood monocytes and guinea pig (GP) resident peritoneal macrophages. Response (or increase in C synthesis) to LPS, muramyl dipeptide or lymphokine in vitro, and the role of adherence in this process will be examined. Cells from GP with inflammation will also be studied. Finally, peripheral blood monocytes will be obtained from patients with rheumatoid arthritis or pulmonary tuberculosis. The cells will be assessed in vitro for their capacity to synthesize C2, as well as other characteristics of stimulated cells.